Tuesday, November 4, 2025 11/4/2025

Sex differences in microglia-neuron-circuit interactions in adolescence

Award Number: R01MH128176
ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 12/20/2021
PERIOD OF PERFORMANCE END DATE: 11/30/2026

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Sex differences in microglia-neuron-circuit interactions in adolescence - A basic understanding of neuron-glia interactions is key to linking altered immune function to disrupted neural circuitry and cognition present in major psychiatric diseases. Microglia are a resident immune cell in the cerebral cortex, and one of their main functions under physiological conditions is to modify synaptic connections among neurons. How these activities extend to influence higher-order functional networks in cortical circuits is not clear, particularly in brain regions crucial for cognitive function, such as the prefrontal cortex (PFC). A key may lie in how neural circuit synchrony stimulates nearby microglial cell motility – i.e. active extension and retraction of fine cellular processes – and, specifically, in how this relationship changes throughout adolescence, a critical period for the development of PFC and higher cognition. Further, sex differences have been established in some aspects of microglial function. Clarifying how sex modulates the role of microglia in PFC circuit development is essential, especially given the dramatic sex differences in vulnerability to adolescent onset of psychiatric diseases such as schizophrenia. The goal of the current project is to obtain a basic understanding of glial-neuronal-circuit interactions in the mammalian prefrontal cortex. The planned approach (Aim 1) employs three-dimensional two-photon microscopy and single neuron optogenetics in awake mouse medial prefrontal cortex (mPFC) to elucidate how the structural dynamics of microglial cells are driven by neuronal activity and oscillatory synchrony in local circuits. This will be examined at distinct time windows from pre-adolescence into early adulthood and compared between males and females. (Aim 2,3) To test whether, how, and when microglia activity is necessary for the establishment of adult mPFC function, microglia will be selectively eliminated during restricted windows during adolescence and early adulthood using a pharmacological strategy. Then in adulthood, sex- and adolescent-period specific effects on the development of i) (Aim 2) spatiotemporal circuit dynamics in mPFC (functional network clustering, gamma oscillations, theta-gamma coupling) will be measured using two-photon calcium imaging and dense electrical recordings and ii) (Aim 3) PFC-dependent cognition will be assessed with an established odor-based attentional set-shifting task. This project employs state-of-the-art optical techniques to study brain function of behaving animals with cell- level precision. Results will identify when and how microglia interact with developing neuronal circuits to support adult-level cognitive function under physiological conditions. Since microglia may be a key mediator of psychiatric disease-relevant neuroimmune dysfunction, the basic science insights from this project, particularly afforded by a sex- and developmental-period stratified approach, could transform the search for core pathophysiological mechanisms and circuit-based treatments.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2025 ( Subtotal = $350,836 )
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	005	4	4/21/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$43,905
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	003	4	1/3/2025	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$0
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	002	4	12/30/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	-$61,914
2025	2025	RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC.	140 OLD ORANGEBURG RD BLDG 35	ORANGEBURG	NY	10962	ROCKLAND	USA	Mental Health Research Grants	001	4	12/23/2024	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$412,750
2025	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	3	12/20/2024	NON-COMPETING CONTINUATION	$0
2025	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	004	3	4/21/2025	NON-COMPETING CONTINUATION	-$43,905
														Subtotal = $350,836

Issue Date FY: 2024 ( Subtotal = $390,000 )
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	3	12/18/2023	NON-COMPETING CONTINUATION	$351,000
2024	2024	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION INC	58 EDGEWOOD AVE NE	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	001	3	8/15/2024	NON-COMPETING CONTINUATION	$39,000
														Subtotal = $390,000

Issue Date FY: 2023 ( Subtotal = $386,080 )
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	001	2	3/1/2023	NON-COMPETING CONTINUATION	$38,608
2023	2023	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	2	12/1/2022	NON-COMPETING CONTINUATION	$347,472
														Subtotal = $386,080

Issue Date FY: 2022 ( Subtotal = $345,200 )
2022	2022	GEORGIA STATE UNIVERSITY RESEARCH FOUNDATION, INC.	58 EDGEWOOD AVE NE 3RD FL	ATLANTA	GA	30303	FULTON	USA	Mental Health Research Grants	000	1	12/17/2021	NEW	$345,200
														Subtotal = $345,200

Grand Total All Awards = $1,472,116

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Sex differences in microglia-neuron-circuit interactions in adolescence

Award Number: R01MH128176

ORGANIZATION: NATIONAL INSTITUTE OF MENTAL HEALTH

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 12/20/2021

PERIOD OF PERFORMANCE END DATE: 11/30/2026

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